Electronic Resonant Stimulated Raman Scattering Microscopy for Ultrasensitive Vibrational Imaging

在化学系化学测量和成像计划的支持下，哥伦比亚大学的魏敏教授正在开发新的测量方法，这些方法有可能提供关于单个分子的化学信息，这是测量科学的终极能力。拉曼光谱和显微镜是测量分子化学性质的常用工具，因为这些工具使研究发现和化学评估成为可能，这对工业、医疗保健、材料和生物研究以及环境监测都有价值。然而，传统的拉曼方法受到限制，因为需要许多分子来产生与背景足够不同的拉曼信号，这被称为检测极限。Min教授正在通过一种前所未有的方法提高拉曼显微镜的检测极限，这样单个分子就可以在常规的基础上进行化学表征，同时存在于各种化学和生物环境中。Min教授和他的团队使用这种新型的拉曼显微镜来同时获得在生物细胞内发现的许多物种的图像，以及研究单个酶的行为，从而促进我们对复杂生物世界的理解。Min Group正在利用他们在光谱学和显微镜方面的专业知识，开发演示和教育实验室实验，让当地高中和社区大学中未被充分代表的少数族裔学生参与进来，目标是提高学生的物理技能，并提高他们对未来科学和工程职业的兴趣。这些新仪器和实验室的影响通过高影响力的、基于互联网的教学视频在线传播而被放大。拉曼光谱提供了关于分子结构和与环境相互作用产生的动力学的精细化学信息。不幸的是，拉曼信号在光学远场中本质上是微弱的。虽然已建立的表面增强拉曼光谱的近场方法可以提供极高的检测极限，但近场方法严格依赖于目标分子与金属纳米结构的紧密相互作用，限制了它们在选定的一组化学和生物体系中的应用。该项目解决了对超低检测下限拉曼显微镜的迫切需求，而不依赖于纳米结构。Min教授和他的团队将共振拉曼光谱与受激拉曼散射显微镜相结合，实现了超低检测极限的振动成像。由于电子共振放大和受激拉曼放大的共同作用，拉曼散射截面提高了几个数量级，使单分子检测成为可能。Min教授和他的团队在生物细胞内部的多波长成像以及单分子、酶催化的生化反应的机械研究中使用了新的超低检测极限拉曼显微镜方法。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Wei Min of Columbia University is developing new measurement methods that have the potential to provide chemical information on individual molecules, the ultimate capability in measurement science. Raman spectroscopy and microscopy are popular tools for measuring chemical properties of molecules, as these tools enable research discoveries and chemical assessments, which are of value to industry, health care, materials and biological research, and environmental monitoring. However, conventional Raman methods are restricted, in that many molecules are required to generate a Raman signal sufficiently different from the background, which is referred to as the detection limit. Professor Min is improving the detection limit of Raman microscopy through an unprecedented approach, such that individual molecules can be chemically characterized on a routine basis, while present in a variety of chemical and biological environments. Professor Min and his team use this new form of Raman microscopy to simultaneously obtain images of many species found inside biological cells, as well as study the behavior of individual enzymes, thereby facilitating our understanding of the complex biological world. The Min group is leveraging their expertise in spectroscopy and microscopy to develop demonstrations and educational laboratory experiments that engage underrepresented minority students in local high schools and community colleges, with the goal being enhancement of student physical science skills and interest in future careers in science and engineering. The impact of these new instruments and labs is amplified by online dissemination through high-impact, internet-based instructional videos.Raman spectroscopy provides exquisite chemical information about molecular structure and dynamics resulting from interactions with the environment. Unfortunately, Raman signals are intrinsically weak in the optical far field. Although established near-field methods of surface-enhanced Raman spectroscopy can offer superb limits of detection, the strict reliance of near-field approaches on close interaction of target molecules with metallic nanostructures limits their application to a select group of chemical and biological systems. The project addresses the urgent need for ultra-low-limit-of-detection Raman microscopy, without relying on nanostructures. Professor Min and his team combine resonance Raman spectroscopy with stimulated Raman scattering microscopy to achieve ultra-low-limit-of-detection vibrational imaging. This enabling technology results from enhancement of the Raman scattering cross section by several orders of magnitude, due to the joint action of electronic resonant amplification and stimulated Raman amplification, making possible single-molecule limits of detection. Professor Min and his team employ the new ultra-low-limit-of-detection Raman microscopy method in multi-wavelength imaging of the interior of biological cells, as well as in mechanistic studies of single-molecule, enzyme-catalyzed biochemical reactions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.